The present invention relates to processes for the preparation of phosphatide-salt complexes. In particular, the present invention relates to processes for the preparation of phosphatidylserine-salt complexes and phosphatidic-acid-salt complexes using carboxylate-salt complexes that are reacted in aqueous systems.
Phosphatidylserine salts and phosphatidic-acid salts are used in pharmaceutical compositions, nutritional compounds, and functional foods. The importance of phosphatidylserine as a functional ingredient is supported by the US FDA's qualified health claims in which the usage of phosphatidylserine was related to the reduction of cognitive dysfunction and dementia in the elderly.
Rutenberg, in U.S. Pat. No. 6,410,522 (assigned to the assignee of the present invention and hereby incorporated by reference as if fully set forth herein), teaches an anti-depressant, stress suppressor, and mood improver having a prominent action for decreasing blood cortisol level and serotonin reuptake, and has an effect of alleviating symptoms associated with depression and mental & emotional stress of a subject administered with the improver.
De Ferra et al., in U.S. Pat. No. 6,492,146 (hereinafter De Ferra '146), disclose a process for the preparation of phosphatidylserine (PS) with racemic or enantiomerically pure serine in the presence of the enzyme phospholipase-D (PLD) and a surfactant in a quantity not greater than 0.4 grams per gram of substrate in which the reaction medium is an aqueous dispersion free of organic solvents. According to De Ferra '146, the main advantage of the process is the possibility to carry out the transphosphatidylation reaction of phosphatidylcholine, and of similar phosphatides in an aqueous medium, to obtain phosphatidylserine of good purity with highly-satisfactory yields and with minimal phosphatidic acid (PA) by-product.
Schmitt et al., in Patent DE 19917249 (hereinafter Schmitt '249), disclose a process for the preparation of PS salt by adding L-serine to an aqueous dispersion of lecithin (1-20% w/w), adding a PLD and CaCl2 solution to the dispersion, stiffing the mixture at room temperature for 10-20 hours, separating the resulting PS—Ca salt from the aqueous phase, washing the Ca salt with water to remove L-serine and extracting the product with ethanol.
Typically, a solvent is used to completely dissolve the lecithin in transphosphatidylation reactions. A dissolved solution, as opposed to a suspension, makes the process easier to manage. Alternatively, in aqueous medium, surfactant is used to enable a manageable solution/dispersion of the lecithin substrate.
It would be desirable to have processes for the preparation of phosphatide-salt complexes in which the transphosphatidylation reaction is carried out in a solvent-free, aqueous medium for enabling the production and separation of phosphatide-salt complexes with no need for further costly extraction of surfactant material from the reaction mixture with solvents.